Purified vitexin compound 1, a new neolignan isolated compound, promotes PUMA‐dependent apoptosis in colorectal cancer

Abstract

Purified vitexin compound 1 (VB1, a neolignan isolated and extracted from the seed of Chinese herb Vitex negundo) is an effective antitumor agent and exhibits promising clinical activity against various cancers including colorectal cancer. However, it remains unknown about the precise underlying mechanism associated with the antitumor effect of VB1 and how it triggers apoptosis in cancer cells. Here, we demonstrated that VB1 promoted apoptosis via p53‐dependent induction of p53 upregulated modulator of apoptosis (PUMA) and further to induce Bax (Bcl‐2‐associated X protein) activation and mitochondrial dysfunction in colon cancer HCT‐116 and LoVo cells. Deficiency in p53, PUMA, or Bax abrogated VB1‐induced apoptosis and promoted cell survival in HCT‐116 cells. Furthermore, the combination of VB1 with chemotherapeutic drugs 5‐fluorouracil (5‐FU) or NVP‐BZE235 resulted in a synergistic antitumor effect via PUMA induction in HCT‐116 cells. VB1 significantly suppressed the cell proliferation of wild‐type (WT) HCT‐116 and LoVo cells in vitro and tumor growth in vivo. The results indicate that p53/PUMA/Bax axis plays a critical role in VB1‐induced apoptosis and VB1 may have valuable clinical applications in cancer therapy as a novel anticancer agent used alone or in combination with other chemotherapeutic drugs.

SIRT6, a novel direct transcriptional target of FoxO3a, mediates colon cancer therapy

“…The activity of caspase-3/9 was determined by Western blot using both cleaved- and full-length of caspase9/3 antibodies. For analysis of apoptosis by flow cytometry, Annexin V-FITC and PI were used to stain cells after treatment, which were then detected by flow cytometry as described before 33.…”

“…The tumors were measured every other day. Immunohistochemistry analysis was performed on paraffin sections, as described 33.…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Caused cell cycle arrest at the G2/M phase [399]. Vitexin + 5-fluorouracil had synergistic anti-tumor effects via PUMA induction [402]. Vitexin + Doxorubicin + Sorafenib induced apoptosis [405].…”

“…Vitexin has shown anticancer effects in several colon cancer models. Chen et al [402] showed that vitexin promoted apoptosis through p53, p53 upregulated modulator of apoptosis (PUMA) and Bax (Bcl-2-associated X protein) activation. When vitexin was combined with the anticancer agent 5-fluorouracil, a synergistic antitumor effect via PUMA induction was observed.…”

Natural Products as Modulators of Sirtuins

“…Several structurally diverse natural products ranging from polyphenols to chromone-derived compounds, and flavonoids to chalchones, have shown to possess stimulatory or inhibitory effects on different sirtuin isoforms. Apart from preclinical [ 128 ] and mode of action studies [ 129 , 130 , 131 ] of known sirtuin inhibitors/modulators towards drug discovery, several sirtuin inhibitors and modulators from natural sources have undergone clinical trials. In this chapter, we will report the therapeutic importance of the natural products or natural NP-derived compounds that are active on Sirtuins.…”