Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

Natural products (NPs) are useful sources of bioactive compounds and play important roles in the development and discovery of new drugs for diverse human diseases. Most natural products originate from terrestrial species, but diverse marine organisms are another source of new agents for cancer therapy. Natural products derived from marine organisms show diverse pharmacological activities via bioactive secondary metabolites. They regulate biological activities, such as cell proliferation, cell viability, induction of ROS production, ER stress, and apoptosis via modulation of cellular mechanisms in many cancers. Many natural products isolated from marine species require further study to elucidate the efficacy of their biological activity and anticancer effects. In this review, we summarize the biological properties and anticancer effects of diverse natural products extracted from marine organisms and their roles in tumor therapy. Cancer is one of the leading causes of death and an economic burden worldwide (1). Cancer involves an abnormal proliferation of cells and tissues, and is affected by various risk factors such as age, diet, genetics, and environmental factors (2, 3). It is also caused by the mutation of several cancer-related genes called tumor suppressors and oncogenes (4). Cancer also presents the ability of metastasis and recurrence, which are difficult to treat (5). Although conventional anticancer therapy includes both chemotherapy to induce apoptosis of target cancer cells and surgical therapy to remove tumors, these methods are limited by issues of therapeutic efficacy, safety, and side effects. Thus, it is necessary to develop novel strategies for cancer therapy, and natural products (NPs) are a promising source for novel drug development because they show diverse biological activities and anticancer effects via inhibition of tumor growth by interacting with several signaling pathways (6, 7). NPs have been a useful source of bioactive compounds and play an important role in the discovery and development of drugs. Most NPs, originated from terrestrial microbes, fungi, and plants, have been discovered to possess many pharmacologically active factors and used to treat several human diseases. Some of these are utilized as clinically valuable drugs for anticancer therapy (8-10). However, marine organisms have recently attracted substantial attention because 70% of the earth is covered by water, representing 95% of biodiversity (11-13). NPs derived from marine organisms have been researched for novel bioactive secondary metabolites due to their diverse pharmacological activities. Marine environments are estimated to harbor more than one million species and one billion different types of marine microbes (14). Today, around 28,000 new compounds isolated from marine species, such as algae, seaweed, sponges, and starfish, have been reported, and this species diversity provides a diverse array of secondary metabolic products (15, 16). In this review, we present NPs derived from marine environments, and summari...

Human mesenchymal stem cells (hMSCs) are a potent source of cell-based regenerative therapeutics used to treat patients with ischemic disease. However, disease-induced oxidative stress disrupts mitochondrial homeostasis in transplanted hMSCs, resulting in hMSC apoptosis and reducing their efficacy post-transplantation. To address this issue, we evaluated the effects of melatonin on cellular defense mechanisms and mitophagy in hMSCs subjected to oxidative stress. H2O2-induced oxidative stress increases the levels of reactive oxygen species and reduces membrane potential in hMSCs, leading to mitochondrial dysfunction and cell death. Oxidative stress also decreases the expression of 70-kDa heat shock protein 1L (HSPA1L), a molecular chaperone that assists in the recruitment of parkin to the autophagosomal mitochondrial membrane. Decreased expression of HSPA1L destabilizes parkin, thereby impairing mitophagy. Our results indicate that treating hMSCs with melatonin significantly inhibited mitochondrial dysfunction induced by oxidative stress, which decreased hMSCs apoptosis. In damaged hMSCs, treatment with melatonin increased the levels of HSPA1L, which bound to parkin. The interaction between HSPA1L and parkin increased membrane potential and levels of oxidative phosphorylation, resulting in enhanced mitophagy. Our results indicate that melatonin increased the expression of HSPA1L, thereby upregulating mitophagy and prolonging cell survival under conditions of oxidative stress. In this study, we have shown that melatonin, a readily available compound, can be used to improve hMSC-based therapies for patients with pathologic conditions involving oxidative stress.

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Background/Aim: Anti-cancer drug resistance restricts the efficacy of chemotherapy in malignant tumors. Casein kinase 2α (CK2α) is highly expressed in 5fluorouracil (5FU)-resistant colorectal cancer (CRC) cells. We hypothesized that inhibition of CK2α might reduce CRC resistance to 5FU. Materials and Methods: To investigate the role of CK2α in 5FU-resistant CRC cells, we assessed cell viability, apoptosis, cyclin-dependent kinase 4 (CDK4) activity, cell-cycle progression, invasion, and sphere formation in 5FU-resistant CRC cells. Results: CK2α levels were significantly increased in 5FU-resistant CRC cells compared to those in wild-type CRC cells. During exposure to 5FU, viability, CDK4 activity, cell-cycle progression, invasion, and sphere formation were enhanced, while apoptosis was decreased in 5FU-resistant CRC cells. These effects were mediated by the inhibiting effects of CK2α on endoplasmic reticulum (ER) stress. Combination of CK2α knockdown with 5FU treatment promoted apoptosis of 5FUresistant CRC cells by inducing ER stress. Conclusion: 5FU treatment in combination with a CK2α inhibitor may exert a synergistic effect against drug-resistant cancer cells.Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, and the second leading cause of cancer-related mortality (1). Although anti-cancer chemotherapy is a promising treatment strategy for CRC, anti-cancer drug resistance limits its clinical outcomes, resulting in cancer-related death (2, 3). Thus, to address drug resistance to single-agent chemotherapy, polychemotherapy regimens with non-overlapping mechanisms of actions have been employed, leading to enhanced therapeutic efficacy in several tumor types, such as lymphoma, breast cancer, and testicular cancer (4). However, these polychemotherapies, as well as surgical therapy (5) and radiotherapy (6), do not address all cancer types. Novel therapeutic strategies have emerged to attack key characteristics of tumors, including targeted therapy. In particular, a combination of targeted therapy with chemotherapy is a promising strategy for overcoming drug resistance and effectively treating CRC.Casein Kinase 2 (CK2), consisting of 2 large catalytic subunits, CK2α (44 kDa) and CK2α' (36 kDa), and 2 small non-catalytic CK2β (25 kDa) subunits, is a constitutively active protein kinase that phosphorylates hundreds of substrates. The expression and activity of CK2, particularly the CK2α subunit, are usually increased in cancer cells, where CK2 exerts anti-apoptotic, pro-migratory, and proproliferative effects (7, 8). In CRC, CK2 has been implicated in cancer progression and anti-cancer drug resistance (9). In addition, a previous study demonstrated that CK2 suppresses the endoplasmic reticulum (ER) stress response, leading to down-regulation of programmed cell death in cancer cells (10). These findings indicate that CK2 plays pivotal roles in CRC characteristics, including cancer cell survival, invasion, progression, and drug resistance.In the present study, we investigated the ability of ...