World Journal of Pharmacology and Toxicology
Open Access

Deregulation of apoptosis signaling is a necessary function of most cancers cells and performs an integral function in tumorigenesis. Xanthohumol is an active ingredient in typical Chinese medicines hops (humulus lupulus l). Recently studies have shown the profound anti-tumor activities of xanthohumol in multiple cancer models. However, its efficiency in non-small cell lung cancers (NSCLC) and the underlying mechanisms are nonetheless elusive. Here, we have investigated the efficiency of xanthohumol towards NSCLC cells in vitro and xenograft mouse models. Xanthohumol suppressed cell viability, colony formation and triggered apoptosis in a549, h520, and h358 cells [1].

Xanthohumol activated mitochondrial apoptosis through upregulation of (p53-upregulated modulator of apoptosis) puma expression. After xanthohumol treatment, the akt activity was inhibited, which resulted in dephosphorylation of foxo3a and puma induction. Silent puma or foxo3a impaired xanthohumol-induced apoptosis in NSCLC cells. In nude mice, xanthohumol administration suppressed NSCLC xenograft tumor increase and extended puma expression in tumor tissues. Briefly, our research published a novel mechanism by which xanthohumol exerted its anti-tumor activity in a puma-dependent manner in NSCLC cells [2].

Non-small cell is the most prevalent cancer type worldwide and caused a significant threat to the public’s health. Even superior therapeutic techniques have been developed in the course of the previous decades, some serious negative results of these therapeutics avoided patients from medical benefits. Thus, it is urgent to enhance novel anti-tumor agents with excessive efficacy and low toxicity for NSCLC. Throughout history, natural products have performed a dominant position in the treatment of human diseases, and Over 60% of the current anti-cancer tablets have been derived in one way or any other from herbal sources [3].

In distinction with the compounds obtained through artificial chemistry, herbal compounds, in particular those extracted from ordinary Chinese drugs with long scientific use, have greater structural range and protection profiles. This study found that Xanthohumol exhibited massive anti-tumor activity human NSCLC cells in vivo and in vitro. Xanthohumol dose-dependently upregulated PUMA expression and induced apoptosis in NSCLC cells. Treatment with 10 mg/kg Xanthohumol did not cause a significant body weight loss, indicating Xanthohumol is properly tolerated in vivo. These effects are regular with preceding studies that Xanthohumol exhibited very low or no toxicity in quite a number non-tumor cells, along with human lung fibroblast cells (MRC-5), main human hepatocytes, oligodendrogliaderived cells (OLN-93), and human pores and skin fibroblasts. These effects indicated that Xanthohumol may want to be a protected and positive chemical with a remarkable remedy margin for most cancers cells [4].

PUMA performs a vital role in inducing apoptosis in mammalian cells as a “BH3-only” Bcl-2 family member. PUMA triggers Bax/Bak mitochondrial membrane translocation with the apoptotic stimuli and prompts these proapoptotic indicators by using neutralizing antiapoptotic Bcl-2 family proteins, which eventually causes mitochondrial outer membrane permeabilization (MOMP) and caspase cascade activation. Owing to this important function in apoptosis induction dysfunction of PUMA is regularly associated to apoptotic escape in most cancers cells. Compared to normal tissues, a decrease protein stage of PUMA was once often observed in a couple of cancers, inclusive of ovarian cancer, NSCLC, gallbladder adenocarcinoma, and prostate cancer [5].

In Xanthohumol-treated NSCLC cells, with the upregulation of PUMA, cleaved-caspase3 and -caspase9 had been dramatically increased, suggesting that Xanthohumol activated the mitochondrial apoptosis in NSCLC cells. Moreover, Knockdown of PUMA impaired apoptosis similarly validated that the upregulation of PUMA performed a critical position in Xanthohumol-induced apoptosis and tumor suppression. According to previous studies, PUMA was identified as a p53 target gene prompted upon DNA-damaging agent through activation of p53. Later, one-of-a-kind mechanisms have been recognized to be concerned in PUMA regulation.

PUMA was once determined to be promoted with the aid of different transcription elements like FoxO3a even barring DNA injury response. In that case, the upregulation of PUMA is independent of p53, NF-kB or p73. This learn about located that Xanthohumolinduced PUMA expression in quite a number NSCLC cells with no difference, together with wild type, mutant or knockout p53 cell. These effects indicated that Xanthohumol-upregulated PUMA expression is impartial of transcription thing p53. Furthermore, our records published that suppression of Akt-FOXO3a axis via Xanthohumol or by using inhibitor notably accelerated PUMA protein level.

In contrast, exogenous overexpression of lively Akt inhibited Xanthohumol-mediated PUMA induction, indicating suppression of Akt endeavor is required for PUMA expression after Xanthohumol treatment. Moreover, we located that knockdown of FOXO3a compromised Xanthohumol-induced PUMA and apoptosis in NSCLC cells, in addition demonstrated that the Akt-FOXO3a axis performs an essential function in PUMA expression. In summary, the current find out about tested the anti-tumor impact of Xanthohumol in NSCLC cells and determined a novel mechanism via which Xanthohumol exhibited its activities.

I would like to acknowledge Central South University Third Xiangya Hospital, Changsha, Hunan, China for giving me an opportunity to do research.

No potential conflicts of interest relevant to this article were reported.

1. Skoulidis F, Heymach JV (2019) Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer 19: 495-509.

Indexed at, Google Scholar, Crossref

2. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK (2014) Non-small-cell lung cancers: a heterogeneous set of diseases.Nat Rev Cancer 14: 535-546.

Indexed at, Google Scholar, Crossref

3. Naltet C, Besse B (2021) Immune checkpoint inhibitors in elderly patients treated for a lung cancer: a narrative review. Transl Lung Cancer Res 10: 3014-3028.

Indexed at, Google Scholar, Crossref

4. Gieroba B, Arczewska M, Brych AS, Rzeski W, Stepulak A, et al. (2020) Prostate and breast cancer cells death induced by xanthohumol investigated with Fourier transform infrared spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc 231: 118112               

Indexed at, Google Scholar, Crossref

5. Kang Y, Park MA, Heo SW, Park SY, Kang KW, et al.(2013) The radio-sensitizing effect of xanthohumol is mediated by STAT3 and EGFR suppression in doxorubicin-resistant MCF-7 human breast cancer cells.Biochim Biophys Acta 1830: 2638-2648.

Indexed at, Google Scholar, Crossref