Skip to main content

Anti-tumor effects of the American cockroach, Periplaneta americana

Abstract

Since the incidence of cancer has been on the rise due to increasing exposure to various carcinogenic factors in recent years, cancer has gradually become the first killer to the health of human beings. A growing attention has been paid to anti-cancer effects of traditional Chinese medicine (TCM) with low toxicity and good efficacy. As a kind of TCM, Periplaneta americana (P. americana) has a good effect on clinical application, and its anti-tumor effects has been increasingly well studied. In this review, the research progress on the anti-tumor effects of P. americana was summarized. The main mechanisms of its anti-tumor effects include suppression of tumor cell growth, induction of cell cycle arrest and tumor cell apoptosis, inhibition of angiogenesis, enhancement of immunity, and reversal of tumor drug resistance. This review aims to provide an overview of the research on anti-tumor effects of P. americana and aids in its further application as an anti-tumor drug.

Background

As one of the leading causes of death in the world, cancer has been the focus of extensive research [1]. According to GLOBOCAN 2012, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide [2]. Meanwhile, there were approximately 3.4 million cancer patients in China in 2012, and the number of cancer deaths was about 2.46 million [3]. Cancer can seriously threaten the patients’ quality of life and their survival. Surgery, radiotherapy, and chemotherapy are widely used for the treatment of cancer in the world. However, these methods cannot effectively change the causal interaction of individual factors related to the pathological process. Therefore, it is difficult to completely inhibit tumor recurrence and metastasis. Long-term treatment with these methods may facilitate drug resistance and cause serious side effects in patients [4]. Traditional Chinese medicine (TCM) has a well-established history of high efficiency and low toxicity [5,6,7,8]. Tumor treatment with TCM is carried out through the overall regulation of the body [9]. In recent years, cancer therapy using TCM with characteristics of multi-level, multi-link, and multi-target has garnered increasing attention [10,11,12,13].

Periplaneta americana, more commonly known as the American cockroach, is the part of Insecta class, Dictyoptera order, and Blattidae family. It is one of the largest, strongest, oldest, and most successful breeding insect groups [14]. The dried worms or fresh adults of P. americana are often used as a TCM drug [15]. Its taste is salty and acrid, and its nature is cold. These features can promote blood circulation, remove blood stasis, help digestion, aid in detoxification, and induce diuresis for treating edema. P. americana can also be used to treat infantile malnutrition, tonsillitis, body phlegm, carbuncles, sore throat, and insect bites. Modern pharmacological research has revealed that P. americana has anti-tumor effects, and is able to enhance immunity, promote tissue repair, stabilize blood pressure, improve microcirculation, protect the liver, and act as an anti-inflammatory, anti-bacterial, and anti-viral agent as well as an analgesic and antioxidant [15, 16].

Clinical application of P. americana

Active ingredients isolated from P. americana have been developed into clinical drugs in China [17], such as “Xiaozheng Yigan Tablet”, “Kangfuxin Liquid”, “Ganlong Capsule”, and “Xinmailong Injection”. “Xiaozheng Yigan Tablet” is an oral tablet with potent anti-tumor effects and anti-bacterial activity. It has been reported to reduce liver inflammation, promote the recovery of liver function, and reduce the degree of liver fibrosis in patients with hepatitis B virus (HBV) infection [18]. Moreover, it has been revealed in a study with 66 cases of primary liver cancer treated with “Xiaozheng Yigan Tablet” that the level of alpha-fetoprotein was reduced and survival time of patients was prolonged [19]. “Kangfuxin Liquid” has been used in clinic for more than 20 years. The main functions of “Kangfuxin Liquid” include eliminating inflammation, reducing swelling, promoting cell proliferation and growth of new granulation tissue, and promoting organism recover. It is mainly applied for stomach and duodenal ulcer, pressure sores, wounds, and burns. Though the curative effect of “Kangfuxin Liquid” is good, its obvious side effects have not been found [20]. “Ganlong Capsule” has a good anti-hepatitis B virus effect and is characteristic of low price, convenient administration, and little side effect [21]. “Xinmailong Injection” has a wide range of therapeutic effects on the cardiovascular system, including improving microcirculation, expanding pulmonary vessels, diuresis, anti-arrhythmic, inhibiting free radical damage, and anti-atherosclerosis. Clinical trials have demonstrated that “Xinmailong Injection” has good therapeutic effect in congestive heart failure and chronic pulmonary heart disease, and the total effective rate is more than 80%. In addition, no obvious untoward reaction was found during treatment [22]. The clinical application of these drugs continue to increase due to limited adverse reactions [16]. Especially, the effect of P. americana on anti-tumor and immune regulation has attracted widespread attention and increasingly become the research focus [23].

Chemical constituents of P. americana

Numerous studies have shown that the main chemical constituents of P. americana include pheromones, proteins, fatty acids and esters, amino acids, alkaloids, alkanes, polysaccharides, isoflavones, cockroach oil, and peptides [16, 24,25,26,27,28,29,30,31]. It was reported that the 50 components of P. americana were separated and identified, most of which were unsaturated fatty acids and esters [26]. Ten cyclic peptides were isolated and purified from P. americana, eight of which were isolated for the first time [27]. Another study identified 23 compounds in P. americana including 16-hydro-7-hexadecenoic acid lactone (35.98%), fatty acids and esters (26.62%), aliphatic aldehyde, stigmast-4-ene-3-one, alkanes, palmitic acid, and linoleic acid [28]. 19 compounds were also separated and identified from P. americana, which mainly included alkanes, octadecadienoic acid, and octadecadienoic alcohol [29]. P. americana contains more than 16 amino acids, including 7 human essential amino acids and two human semi-essential amino acids [30]. The 70% ethanol extract of P. americana contains amino acid, alkaloid, fatty acids and esters, and pheromones [25]. More than 50 neuropeptides have been identified from P. americana, including allatostatins, pyrokinins, fraps, kinins, and periviscerokinins [31]. In addition, P. americana also contains polysaccharides, cockroach acid, cockroach oil, allergens, chitosan, cytochromes A, B, and C [16, 27].

Pharmacological activity of P. americana

A large number of studies have shown that P. americana has anti-tumor, anti-bacterial, anti-viral, anti-radiation, detumescence, analgesic, and anti-inflammatory effects. In addition, P. americana was shown to protect the liver, promote blood vessel growth, aid in tissue repair, improve microcirculation, and enhance immunity. P. americana also possesses a high antioxidant capacity demonstrated by the clearance of 2,2-diphenylpicrylhydrazyl and OH free radicals [15, 32]. In recent years, the anti-tumor activity of P. americana has become a research focus.

Anti-tumor effects of P. americana

Accumulating evidences have revealed the anti-tumor effects of P. americana on a variety of cancer cells. Herein, we summarized the reported the mechanisms underlying the anti-tumor effects of P. americana.

Inhibition of tumor cell growth

Studies have shown that some TCM drugs can inhibit the growth of tumor cells in vitro and in vivo [12, 33, 34]. These drugs can be used at various stages of tumorigenesis. Mechanistically, these treatments can inhibit the synthesis of DNA, RNA, and proteins, and block the energy metabolism of tumor cells [35]. A previous study has showed that CII-3 from the P. americana caused cytotoxicity in two human lung cancer cell lines [36]. Moreover, P. americana extract inhibited the growth of three human reproductive system cancer cell lines and three human respiratory system tumor cell lines [37, 38]. In addition, P. americana extract suppressed the growth of three human and mouse leukemia cell lines [39]. The 60% ethanol fraction of P. americana organic extracts (PAE60) inhibited tumor growth in S180 tumor-bearing mice by 72.62%. Moreover, PAE60 was determined against 12 human cancer cell lines, and it could effectively inhibited the growth of HL-60, KB, CNE, and BGC823 cells with IC50 values <20 µg/mL [23].

Cell cycle arrest

Cell cycle is a complex process involving multiple factors, such as cyclins, cyclin-dependent protein kinases, and cell cycle-dependent protein kinase inhibitors [40, 41]. The abnormal expression of cyclins and cyclin-dependent protein kinases, and loss of cyclin-dependent protein kinase inhibitors can cause uncontrolled cell proliferation and tumor growth [42]. It has been shown that P. americana extracts can inhibit the growth of progesterone receptor-negative endometrial cancer cells by blocking the cell cycle via up-regulation of p53 expression and down-regulation of C-erbB-2 expression [43]. P. americana extract could arrest the cell cycle of human lung cancer cells H125 in the S phase [44]. Human gastric cancer BGC-823 cells exhibited the cell cycle arrest at G2/M phase in the presence of “Kangfuxin Liquid” that consists of the refined active constituents of P. americana [45]. Moreover, P. americana extract inhibited the growth of Lewis lung carcinoma (3LL) cells in mice and induced cell cycle arrest in G0/G1 phase [46].

Induction of apoptosis

Apoptosis is a process of programmed cell death, which plays a critical role in cancer development and therapies [47,48,49]. Multiple genes are involved in apoptosis in cancer cells, such as pro-apoptotic proteins Fas, Bax, p53 and anti-apoptotic proteins Bcl-2, c-myc [50, 51]. Many natural products can induce apoptosis in various human cancer cells, such as gambogic acid, ursolic acid, vinca alkaloids, and camptothecins [8, 52]. P. americana extract inhibited the proliferation of human hepatoma cells by inducing apoptosis and reducing the mitochondrial membrane potential, up-regulating Bax, Caspase-9, and Caspase-3 expression, and down-regulating Bcl-2 expression [53]. P. americana extracts induced apoptosis in Lewis lung carcinoma (3LL) cells through up-regulation of Fas, Fas receptor (FasR), and p53 gene expression and down-regulation of Bcl-2 expression [54]. In addition, a study revealed that P. americana extract induced apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the mitochondrial pathway [55].

Anti-angiogenic effect

Nutrients and oxygen supplied by the vasculature are essential for tumor growth and metastasis. Thus, angiogenesis plays a vital role in tumorigenesis [56, 57]. Vascular endothelial growth factor (VEGF), a major contributor to angiogenesis, promotes the proliferation and migration of endothelial cells, and increases vascular permeability [58, 59]. P. americana polypeptides significantly inhibited tumor growth, decreased tumor microvessel density (MVD), and reduced VEGF expression [60]. P. americana extract significantly inhibited the tumor growth of H22 tumor-bearing mice and reduced VEGF levels in mice serum [61]. These evidences indicate that the anti-tumor effect of P. americana is probably related to angiogenesis inhibition.

Enhancement of immunity

As an important guarantee for the body health, immunity is closely related to the stability of the internal environment. The homeostasis of the organism is destroyed when the immunity of the organism declines, which contributes to occurrence and spread of tumors [62, 63]. Thus, improving body immunity can achieve anti-tumor effect [64]. Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine with a crucial role in apoptosis, cell survival, and immunity [65, 66]. TNF-α is mainly secreted by monocytes and macrophages and exerts its biological functions through binding to specific receptors on the cell surface and activating intracellular distinct signaling pathways [67]. P. americana polypeptide extracts had a strong inhibitory effect on S180 and H22 tumor-bearing mice. The extracts increased the spleen index and thymus gland index of tumor-bearing mice, promoted the proliferation of T lymphocytes, enhanced the phagocytotic function of macrophages, and up-regulated the levels of IL-2, IL-6, IL-12, and TNF-α [68]. Moreover, P. americana extracts markedly inhibited tumor growth without causing toxicity of immune organs in S180 tumor-bearing mice, which may be related to an increase in TNF-α in the serum of tumor-bearing mice [69]. P. americana could increase the CD4/CD8 ratio of peripheral blood in mice with low immunity [70]. Therefore, P. americana extract showed significant anti-tumor activity that might be related to an enhanced immune function in vivo.

Reversal of drug resistance

Chemotherapy is one of the most common and effective methods in cancer treatment. The advancement of molecular biology, biochemistry, and genetic engineering techniques have led to remarkable achievements in the research and development of anti-tumor drugs. However, drug resistance has become a major obstacle for treatment of cancer [71, 72]. Drug resistance is a complex process involving multiple factors in cancer therapy. Thus, it is urgent and important to improve drug resistance in cancer treatment. There is evidence that P. americana extract effectively reversed the drug resistance of human hepatoma cells by targeting the multidrug resistance protein (MRP), breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) [73]. Additionally, human hepatoma HepG2/ADM cell line has biological characteristics of multi-drug resistance, and P. americana extract could inhibit the growth of HepG2/ADM cells along with reversal of drug resistance [74].

Conclusion

Periplaneta americana extract has been widely applied in China as an alternative medicine against diseases. The above studies have shown that the anti-tumor effects of P. americana are attracting more and more attention. This review aimed to provide a clear picture regarding the anti-tumor effects and the underlying mechanisms of P. americana. The reported mechanisms of anti-tumor effects of P. americana mainly involve inhibition of tumor cell growth, induction of cell cycle arrest and apoptosis, suppression of angiogenesis, enhancement of immunity, and reversal of drug resistance (Fig. 1). However, the specific active constituents and precise mechanisms underlying the anti-cancer activities of P. americana remain uncertain. Thus, it is an important research topic to optimize the extraction process and search for the best technological conditions for further isolation and purification of the anti-tumor constituents of P. americana. Additionally, the mechanisms of anti-tumor effects of P. americana remain to be further identified. More exploration remain to be performed, such as effects of P. americana on cancer metastasis or autophagy. It may be promising to conduct further investigation of PAE60 on the identification of active chemical constituents and relevant pharmacological mechanisms. To be sure, further exploration of anti-cancer drug from P. americana will provide potent scientific basis for clinical use of P. americana and contribute to the development of novel anti-cancer drugs with high efficiency and low toxicity.

Fig. 1
figure 1

Diagraphic illustration of mechanisms of anti-tumor effects of P. americana. P. americana extract inhibited cell proliferation via p53- and C-erbB-2-mediated cell-cycle arrest in progesterone-receptor negative endometrial cancer cells. P. americana extracts induced cell-cycle arrest of Lewis lung carcinoma (3LL) cells and human lung cancer cells H125 at G0/G1 phase and S phase, respectively. “Kangfuxin Liquid” induced cell-cycle arrest of human gastric cancer cells BGC-823 at G2/M phase. P. americana extract decreased the ratio of Bcl-2 to BAX by increasing p53 and upregulated Fas and FasR expression, which induced apoptosis of cancer cells. P. americana may depress angiogenesis by inhibiting VEGF expression and microvessel density (MVD). P. americana extract activated lymphocytes, increased the CD4/CD8 ratio of peripheral blood, prompted T- and B-lymphocytes proliferation, and modulated cytokines release, including TNF-α, IL-2, IL-6, and IL-12. In addition, the extract effectively reversed the drug resistance of human hepatoma cells (HepG2/ADM) by targeting P-gp, MRP, and BCRP

Abbreviations

TCM:

traditional Chinese medicine

VEGF:

vascular endothelial growth factor

TNF-α:

tumor necrosis factor-α

P. americana :

Periplaneta americana

MVD:

microvessel density

HBV:

hepatitis B virus

PAE60:

60% ethanol fraction of Periplaneta americana organic extracts

FasR:

Fas receptor

MRP:

multidrug resistance protein

BCRP:

breast cancer resistance protein

P-gp:

P-glycoprotein

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  3. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.

    Article  PubMed  Google Scholar 

  4. He G, Liu J, Wang J, Xie S. The anti-tumor mechanism research status of traditional Chinese medicine. J Sichuan Tradit Chin Med. 2008;26:47–9.

    Google Scholar 

  5. Liweber M. Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Lett. 2013;332:304–12.

    Article  CAS  Google Scholar 

  6. Xia Q, Mao W. Anti-tumor effects of traditional Chinese medicine give a promising perspective. J Cancer Res Ther. 2014;10(Suppl 1):1–2.

    PubMed  Google Scholar 

  7. Nie J, Zhao C, Deng LI, Chen J, Yu B, Wu X, Pang P, Chen X. Efficacy of traditional Chinese medicine in treating cancer. Biomed Rep. 2016;4:3–14.

    Article  PubMed  Google Scholar 

  8. Tan W, Lu J, Huang M, Li Y, Chen M, Wu G, Gong J, Zhong Z, Xu Z, Dang Y, et al. Anti-cancer natural products isolated from chinese medicinal herbs. Chin Med. 2011;6:27.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Efferth T, Li PC, Konkimalla VS, Kaina B. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med. 2007;13:353–61.

    Article  CAS  PubMed  Google Scholar 

  10. Parekh HS, Liu G, Wei MQ. A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol Cancer. 2009;8:21.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Li X, Yang G, Zhang Y, Yang J, Chang J, Sun X, Zhou X, Guo Y, Xu Y, Liu J, Bensoussan A. Traditional Chinese medicine in cancer care: a review of controlled clinical studies published in Chinese. PLoS ONE. 2013;8:e60338.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Ye L, Jia Y, Ji KE, Sanders AJ, Xue K, Ji J, Mason MD, Jiang WG. Traditional Chinese medicine in the prevention and treatment of cancer and cancer metastasis. Oncol Lett. 2015;10:1240–50.

    PubMed Central  PubMed  Google Scholar 

  13. Carmady B, Smith CA. Use of Chinese medicine by cancer patients: a review of surveys. Chin Med. 2011;6:22.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Shi W. The medical research advanced on Periplaneta americana. Chin J Ethnomed Ethnopharm. 2012;21:50–1.

  15. Yu S, Zhang H, Zhang T, Liu J. Research advances in pharmacological action and clinical application of Periplaneta americana. J Liaoning Coll Tradit Chin Med. 2016;18:228–30.

    Google Scholar 

  16. He Z, Peng F, Song L, Wang X, Hu M, Zhao Y, Liu G. Advances in chemical constituents and pharmacological effects of Periplaneta americana. Chin J Chin Mater Med. 2007;32:2326–30.

    CAS  Google Scholar 

  17. Dai Y, Zeng M, Xiang P. The medicinal value of cockroaches. Chin Med Mat. 2005;28:848–9.

    Google Scholar 

  18. Ou W, Zhu C, Lin W. Observation of the clinical curative effects of Xiao zheng Yi gan Pian on chronic hepatitis B. Chin J Integr Tradit West Med Liver Dis. 1995;5:12–3.

    Google Scholar 

  19. Chen L. Observation of the curative effect of 66 cases with primary liver cancer treated with Xiao zheng Yi gan Pian. Fujian J Tradit Chin Med. 1986;6:16–7.

  20. Zhang H, Geng F, Shen Y, Liu H, Zhao Y, Zhang C. Research progress of Kangfuxin Ye in pharmacological action and clinical application. Chin J Ethnomed Ethnopharm. 2017;26:57–60.

    Article  Google Scholar 

  21. Du Y, Chen H, Li S, Li Z, Li X, Zhang H, Fang C. The hepatic pharmacological effects of Gan long capsules in vivo. Lishizhen Med Mater Med Res. 2006;17:1369–71.

    Google Scholar 

  22. Zhang L. Pharmacological effect and clinical curative effect of Xinmailong injection. Herald Med. 2001;20:250.

    Google Scholar 

  23. Wang XY, He ZC, Song LY, Spencer S, Yang LX, Peng F, Liu GM, Hu MH, Li HB, Wu XM, et al. Chemotherapeutic effects of bioassay-guided extracts of the American cockroach, Periplaneta americana. Integr Cancer Ther. 2011;10:NP12–23.

    Article  PubMed  Google Scholar 

  24. Jiang L, Li X, Xia C, Chen K, He S, Liu G. Research advance on chemical constituents and anti-tumor effects of Periplaneta americana. Med Plant. 2012;3:95–102.

    Google Scholar 

  25. Jiang W, Luo S, Wang Y, Wang L, Zhang X, Ye W. Chemical constituents of Periplaneta americana. J Jinan Univ. 2015;36:294–301.

    Google Scholar 

  26. Yu X, Xu L, Chen S, Sun Q, Zhang D. Analysis of supercritical carbon dioxide extraction of Periplaneta americana by GC-MS. J Luzhou Med Coll. 2016;39:344–6.

    Google Scholar 

  27. Li Y, Wang F, Zhang P, Yang M. Studies on chemical constituents of Periplaneta american. Chin Med Mat. 2015;38:2038–41.

    CAS  Google Scholar 

  28. Luo J, Xiao H, Dong G, Liu G. Analysis of the fat-soluble components in Periplaneta americana by GC-MS. Chin J Ethnomed Ethnopharm. 2009;18:26–7.

    CAS  Google Scholar 

  29. Meng S, Xiao X, Wang S, Luo C, Liu X. Liposoluble chemical constituents of periplaneta americana by GC-MS. Cent South Pharm. 2008;6:23–5.

    CAS  Google Scholar 

  30. Yao L. Study on the chemical ingredients of cockroach-preliminary analysis of amino acid composition. Tianjin Pharm. 1994;6:26–8.

    Google Scholar 

  31. He Z, Liu G, Wang X, Yang L, Zhao Y. Research advance on neuropeptides from Periplaneta americana. Nat Prod Res Dev. 2008;20:180–6.

    CAS  Google Scholar 

  32. Hu Y, Lu X, Wang Y, Peng F. Advances in medicinal value of Periplaneta americana. Med Rev. 2008;14:2822–4.

    Google Scholar 

  33. Xu J, Song Z, Guo Q, Li J. Synergistic effect and molecular mechanisms of traditional Chinese medicine on regulating tumor microenvironment and cancer cells. Biomed Res Int. 2016;2016:1490738.

    PubMed Central  PubMed  Google Scholar 

  34. Mu J, Liu T, Jiang L, Wu X, Cao Y, Li M, Dong Q, Liu Y, Xu H. The traditional Chinese medicine baicalein potently inhibits gastric cancer cells. J Cancer. 2016;7:453–61.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Cheng Y, Zhang L. Study progress on drug research and anti-tumor mechanisms of Chinese medicine. Chin Pharm. 2013;22:103–4.

    CAS  Google Scholar 

  36. Hu Y, Lu X, Liu G, Li M, Peng F. Effect of Periplaneta americana extract on two human lung tumor cell lines. J Pharm Anal. 2011;37:1245–50.

    Google Scholar 

  37. He Z, Hu M, Wang X, Liu G. Toxicity studies of American cockroach extract on three cell strains of human reproductive system cancer cell. Yunnan J Tradit Chin Med Mat Med. 2009;30:56–7.

    Google Scholar 

  38. He Z, Wang X, Yang L, Zhao Y, Liu G. Study on systena genitale tumor cell cytotoxicity of extracts from Periplaneta americana. Northwest Pharm J. 2009;24:271–2.

    Google Scholar 

  39. He Z, Wang X, Hu M, Liu G. The extracts of Periplaneta americana were applied to three human and mouse leukemia cell lines to study the cytotoxicity. Chin J Mod Drug Appl. 2009;30:56–7.

    Google Scholar 

  40. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66.

    Article  CAS  PubMed  Google Scholar 

  41. McDonald ER 3rd, El-Deiry WS. Cell cycle control as a basis for cancer drug development (Review). Int J Oncol. 2000;16:871–86.

    CAS  PubMed  Google Scholar 

  42. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17:93–115.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Zhang X, Zhu Y. Impact of Total Matrine and Periplaneta americana extract on progesterone-receptor negative endometrial cancer cells (JEC). Chin J Chin Mater Med. 2015;40:2210–3.

    CAS  Google Scholar 

  44. Wang J. Effect of Periplaneta americana extract on lung cancer cell H125. Chin J Public Health. 2014;30:1400–2.

    Google Scholar 

  45. Jiang Y, Wang X, Jin C, Yuan F, Liu G, Li S. An experimental study of traditional Chinese medicine Kangfuxin inducing apoptosis in vitro of peptic carcinoma cell line BGC-823. J Kunming Med Coll. 2006;27:5–9.

    Google Scholar 

  46. Jiang Y, Wang X, Jin C, Chen X, Wang Q, Liu G. The inhibitory effect of Periplaneta americana extract on Lewis lung cancer in Mice. J Kunming Med Coll. 2007;5:13–6.

    Google Scholar 

  47. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 2005;5:231–7.

    CAS  PubMed  Google Scholar 

  49. Reed JC. Apoptosis-targeted therapies for cancer. Cancer Cell. 2003;3:17–22.

    Article  CAS  PubMed  Google Scholar 

  50. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55:178–94.

    Article  PubMed  Google Scholar 

  51. Johnson MI, Hamdy FC. Apoptosis regulating genes in prostate cancer (review). Oncol Rep. 1998;5:553–7.

    CAS  PubMed  Google Scholar 

  52. Safarzadeh E, Sandoghchian Shotorbani S, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014;4:421–7.

    PubMed Central  PubMed  Google Scholar 

  53. Wang J, Li X. Mechanism study of Periplaneta americana extract on human hepatoma cells Bel-7402. Chin J Mod Appl Pharm. 2012;29:876–80.

    Google Scholar 

  54. Jiang Y, Wang X, Jin C, Chen X, Li J, Wu Z, Liu G, Li S. Inhibitory effect and mechanism research of Periplaneta americana extract on 3LL lung cancer cell in mice. Chin J Lung Cancer. 2006;9:488–91.

    Google Scholar 

  55. Dong J, Wei Z, Wang J. Apoptosis and the related mechanisms that Periplaneta americana extract on human hepatocellular carcinoma SMMC-7721 cells. Shandong Med J. 2012;52:32–4.

    Google Scholar 

  56. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2:213–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  58. Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549–80.

    Article  CAS  PubMed  Google Scholar 

  59. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803.

    Article  CAS  PubMed  Google Scholar 

  60. Liang G, Zhang D, Zhang H, Liu M. The inhibitory effect of Periplaneta americana polypeptide on tumor growth and angiogenesis in nude mice bearing human hepatocellular carcinoma Bel-7402 cells. Chin J New Drug. 2016;25:687–91.

    CAS  Google Scholar 

  61. Chen J, Geng L, Zhang X, Yang T, Li H, He X, Pu X, Peng F. Effect of Periplaneta americana Extract CII-3 on angiogenesis in H22 hepatoma-bearing mice. J Chin Oncol. 2012;18:274–6.

    Google Scholar 

  62. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.

    Article  CAS  PubMed  Google Scholar 

  63. Terabe M, Berzofsky JA. Immunoregulatory T cells in tumor immunity. Curr Opin Immunol. 2004;16:157–62.

    Article  CAS  PubMed  Google Scholar 

  64. Papaioannou NE, Beniata OV, Vitsos P, Tsitsilonis O, Samara P. Harnessing the immune system to improve cancer therapy. Ann Transl Med. 2016;4:261.

    Article  PubMed Central  PubMed  Google Scholar 

  65. van Horssen R, Ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist. 2006;11:397–408.

    Article  PubMed  Google Scholar 

  66. Parameswaran N, Patial S. Tumor necrosis factor-alpha signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010;20:87–103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang D, Sun Y, Li M, Sun Q, Liu M. Effects of Periplaneta americana polypeptide extracts on tumor growth and immune function in tumor-bearing mice. Chin J New Drug. 2015;24:681–6.

    CAS  Google Scholar 

  69. He X, Pu X, Li J, Peng F. Effect of extractive from Periplaneta americana on immune on and inhibitory tumor action in S180-bearing mice. Chin J Exp Tradit Med Form. 2012;18:179–81.

    CAS  Google Scholar 

  70. Zhou Q, Wu Z, Li Z, Liu J, Wang C. Effect of Periplaneta americana on immune function of mice with low immunity. J Fujian Agricul Forest Univ. 2008;37:519–22.

    Google Scholar 

  71. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53:615–27.

    Article  CAS  PubMed  Google Scholar 

  72. Huang Y, Cole SP, Cai T, Cai YU. Applications of nanoparticle drug delivery systems for the reversal of multidrug resistance in cancer. Oncol Lett. 2016;12:11–5.

    PubMed Central  PubMed  Google Scholar 

  73. Liu J, Xia M, Peng F. Experimental research of Periplaneta americana extract on human drug resistant hepatocellular carcinoma cell line. Chin J Biochem Pharm. 2015;4:19–23.

    Google Scholar 

  74. Qiao T, Niu C, Peng F. Study of Periplaneta americana L. reversing multi-drug resistance of hepatocellular carcinoma. Chin J Biochem Pharm. 2015;4:35–8.

    Google Scholar 

Download references

Authors’ contributions

YZ, PT, and ZH conceived and designed the review. YZ, AY, PT, and ZH wrote the manuscript . All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

Not applicable.

Consent for publication

All of authors consent to publication of this work in Chinese Medicine.

Ethics approval and consent to participate

Not applicable.

Funding

This work was supported by the Excellent Young Scientist Foundation of Beijing University of Chinese Medicine (2015-JYB-XYQ-004).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Pengfei Tu or Zhongdong Hu.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Y., Yang, A., Tu, P. et al. Anti-tumor effects of the American cockroach, Periplaneta americana . Chin Med 12, 26 (2017). https://doi.org/10.1186/s13020-017-0149-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13020-017-0149-6

Keywords