Chaudhry Gul-E-Saba, Md Akim Abdah, Sung Yeong Yik, Sifzizul Tengku Muhammad Tengku
Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Kuala Terengganu, Malaysia.
Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Seri Kembangan, Malaysia.
Front Pharmacol. 2022 Aug 10;13:842376. doi: 10.3389/fphar.2022.842376. eCollection 2022.
Cancer is a multifactorial, multi-stage disease, including complex cascades of signaling pathways-the cell growth governed by dysregulated and abrupt cell division. Due to the complexity and multi-regulatory cancer progression, cancer is still a challenging disease to treat and survive. The screening of extracts and fractions from plants and marine species might lead to the discovery of more effective compounds for cancer therapeutics. The isolated compounds and reformed analogs were known as future prospective contenders for anti-cancer chemotherapy. For example, Taxol, a potent mitotic inhibitor discovered from Taxus brevifolia, suppresses cell growth and arrest, induces apoptosis, and inhibits proliferation. Similarly, marine sponges show remarkable tumor chemo preventive and chemotherapeutic potential. However, there is limited research to date. Several plants and marine-derived anti-cancer compounds having the property to induce apoptosis have been approved for clinical trials. The anti-cancer activity kills the cell and slows the growth of cancer cells. Among cell death mechanisms, apoptosis induction is a more profound mechanism of cell death triggered by naturally isolated anti-cancer agents. Evading apoptosis is the major hurdle in killing cancer cells, a mechanism mainly regulated as intrinsic and extrinsic. However, it is possible to modify the apoptosis-resistant phenotype of the cell by altering many of these mechanisms. Various extracts and fractions successfully induce apoptosis, cell-cycle modulation, apoptosis, and anti-proliferative activity. Therefore, there is a pressing need to develop new anti-cancer drugs of natural origins to reduce the effects on normal cells. Here, we've emphasized the most critical elements: i) A better understanding of cancer progression and development and its origins, ii) Molecular strategies to inhibit the cell proliferation/Carcino-genesis, iii) Critical regulators of cancer cell proliferation and development, iv) Signaling Pathways in Apoptosis: Potential Targets for targeted therapeutics, v) Why Apoptosis induction is mandatory for effective chemotherapy, vi) Plants extracts/fractions as potential apoptotic inducers, vii) Marine extracts as Apoptotic inducers, viii) Marine isolated Targeted compounds as Apoptotic inducers (FDA Approved/treatment Phase). This study provides a potential therapeutic option for cancer, although more clinical studies are needed to verify its efficacy in cancer chemotherapy.
癌症是一种多因素、多阶段的疾病,包括复杂的信号通路级联反应——细胞生长受失调和突然的细胞分裂控制。由于癌症进展的复杂性和多调控性,癌症仍然是一种难以治疗和治愈的疾病。对植物和海洋物种提取物及馏分的筛选可能会发现更多用于癌症治疗的有效化合物。分离出的化合物和改造后的类似物被认为是未来抗癌化疗的潜在竞争者。例如,从短叶红豆杉中发现的强效有丝分裂抑制剂紫杉醇可抑制细胞生长和停滞、诱导细胞凋亡并抑制增殖。同样,海洋海绵显示出显著的肿瘤化学预防和化疗潜力。然而,迄今为止相关研究有限。几种具有诱导细胞凋亡特性的植物和海洋来源的抗癌化合物已获批用于临床试验。抗癌活性可杀死细胞并减缓癌细胞的生长。在细胞死亡机制中,诱导细胞凋亡是天然分离的抗癌药物引发的一种更深刻的细胞死亡机制。逃避细胞凋亡是杀死癌细胞的主要障碍,这一机制主要受内在和外在因素调控。然而,通过改变许多这些机制来改变细胞的抗凋亡表型是可能的。各种提取物和馏分成功诱导细胞凋亡、细胞周期调节、凋亡和抗增殖活性。因此,迫切需要开发新的天然来源抗癌药物,以减少对正常细胞的影响。在此,我们强调了最关键的要素:i)更好地理解癌症的进展、发展及其起源,ii)抑制细胞增殖/致癌作用的分子策略,iii)癌细胞增殖和发展的关键调节因子,iv)细胞凋亡中的信号通路:靶向治疗的潜在靶点,v)为什么诱导细胞凋亡对有效的化疗至关重要,vi)植物提取物/馏分作为潜在的凋亡诱导剂,vii)海洋提取物作为凋亡诱导剂,viii)海洋分离的靶向化合物作为凋亡诱导剂(美国食品药品监督管理局批准/治疗阶段)。本研究为癌症提供了一种潜在的治疗选择,尽管还需要更多的临床研究来验证其在癌症化疗中的疗效。