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自噬和凋亡的双重调节作为结肠癌细胞中[具体物质]抗癌作用机制

Dual Modulation of Autophagy and Apoptosis as Anticancer Mechanism of Action of in Colon Carcinoma Cells.

作者信息

Anifowose Saheed O, Oladejo Musa K, Salih Abdalrhaman M, Almutairi Layali M, Almansour Mansour I, Al-Dahmash Badr, Al Mosallam Mobarak S, Alanazi Ibrahim O, Rady Ahmed

机构信息

Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Botany and Microbiology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

出版信息

Int J Mol Sci. 2025 May 29;26(11):5247. doi: 10.3390/ijms26115247.

Abstract

(Kh) is a medicinal plant with therapeutic properties. Studies have reported on the general bioactivity and anticancer potentials of the plant, but no investigations have yet investigated its anticancer mechanism of action. This study presents the first examination of the anticancer mechanism of action of the methanolic extract of Kh, alongside phytochemical profiling of its anticancer constituents. We conducted in vitro investigations into the mechanism of action of Kh and performed bioactivity-guided fractionation, with subsequent identification of its anticancer phytochemicals using HPLC and GC-MS, respectively. Kh posed a potent antiproliferative effect against colon carcinoma cells and an antioxidant property at low microgram levels. Furthermore, the treatment of Kh in cells led to the accumulation of p62 puncta, indicating inhibition of autophagic flux degradation. Kh impacts microtubule, induced G1 arrest, and late apoptosis induction in cells. Phytochemicals belonging to sesquiterpene alcohols were found most abundant in the Kh bioactive fractions. The identified phytochemicals are potential inducers of apoptosis, autophagy flux inhibition, and G1-phase arrest. Our findings suggest that the anticancer property of Kh is mediated through the dual modulation of autophagy and apoptosis. Further studies are needed to isolate the active compounds responsible for these effects and further elucidate the underlying molecular mechanisms.

摘要

Kh是一种具有治疗特性的药用植物。已有研究报道了该植物的一般生物活性和抗癌潜力,但尚未有研究探究其抗癌作用机制。本研究首次对Kh甲醇提取物的抗癌作用机制进行了研究,并对其抗癌成分进行了植物化学分析。我们对Kh的作用机制进行了体外研究,并进行了生物活性导向的分离,随后分别使用高效液相色谱法(HPLC)和气相色谱 - 质谱联用仪(GC-MS)鉴定其抗癌植物化学物质。Kh在低微克水平下对结肠癌细胞具有强大的抗增殖作用和抗氧化特性。此外,用Kh处理细胞导致p62斑点积累,表明自噬流降解受到抑制。Kh影响微管,诱导细胞G1期阻滞和晚期凋亡。在Kh生物活性组分中发现倍半萜醇类植物化学物质含量最为丰富。鉴定出的植物化学物质是凋亡、自噬流抑制和G1期阻滞的潜在诱导剂。我们的研究结果表明,Kh的抗癌特性是通过自噬和凋亡的双重调节介导的。需要进一步研究分离负责这些作用的活性化合物,并进一步阐明其潜在的分子机制。

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