Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review

Abstract

Background B cell lymphoma-2 (Bcl-2) family members play important roles in cell survival as well as cell death. The role of myeloid cell leukemia-1 (Mcl-1), an important member of the Bcl-2 family, is well established in hematopoietic malignancies. However, the association between Mcl-1 and oral cavity, cancers is not clearly defined. Methods A scoping review was conducted until June 30, 2021, using four major databases, PubMed, Scopus, Web of Science, and Embase. Medical subject headings keywords for Mcl-1, along with its other identifiers, and head and neck cancers (only oral cavity tumors) were used to evaluate the expression, function, molecular association, and therapeutic approach of Mcl-1 in oral cavity cancers and precancers. Findings Mcl-1 expression was associated with the progression of oral cavity cancers. The molecular mechanism and pathways of Mcl-1 in oral cavity cancers established via experimental results have been highlighted in this review. Moreover, the various synthetic and naturally derived therapeutic agents targeting Mcl-1 have been documented. Novelty/Improvement Based on our present review, Mcl-1 appears to be an effective anticancer target that can be used in the therapeutic management of oral cancers.

Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis

“…Mcl-1, a member of the Bcl-2 family with antiapoptotic properties, promotes cell survival by inhibiting apoptosis (20). Our group has previously shown that Mcl-1 is overexpressed in oral cancer and is closely associated with poor clinical outcomes, suggesting that the inhibition of Mcl-1 might be a good strategy for the treatment of oral cancer (21,22). Mcl-1 regulates mitochondrial outer membrane permeabilization, which is a vital process in the initiation of apoptosis, by engaging the interaction with BH3-only proteins, such as Bim, and t-Bid.…”

Podophyllotoxin reduces the aggressiveness of human oral squamous cell carcinoma through myeloid cell leukemia‑1

“…To identify the potent anticancer mechanism of action of PPT in OSCC, apoptosis associated with the Bcl-2 family of proteins, particularly myeloid cell leukemia-1 (Mcl-1) was assessed. In OSCC, the Mcl-1 gene is commonly amplified and upregulated, which affects the clinical course and survival of patients with this disease (21)(22)(23)(24). Mcl-1 is also upregulated and is associated with poor outcomes in other malignant tumors, such as hematologic malignancies (25), breast cancer (26,27), lung (28), and gastric cancer (29).…”

“…Mcl-1 blocks the oligomerization of the pro-apoptotic Bcl-2 family members, Bax and Bak, which sequesters them to produce protein-permeable holes in the mitochondrial outer membrane ( 30 - 32 ). Finally, a reduction in Mcl-1 expression promotes cytochrome C release into the cytoplasm, which activates the caspase cascade and induces apoptosis ( 21 ). Based on these findings, targeting Mcl-1 may represent a promising approach for treating OSCC.…”

Podophyllotoxin enfeebles human oral squamous cell carcinoma through Myeloid cell leukemia-1

“…To identify the potent anticancer mechanism of action of PPT in OSCC, we examined apoptosis associated with the Bcl-2 family, particularly myeloid cell leukemia-1 (Mcl-1). In OSCC, the Mcl-1 gene is commonly ampli ed and upregulated, which affects the clinical course and patient survival [20][21][22][23].…”

“…Bak and Bax, two pro-apoptotic members of the Bcl-2 family, are prevented from oligomerizing by Mcl-1 which sequesters them to produce protein-permeable holes in the mitochondrial outer membrane [29][30][31]. Finally, a reduction in Mcl-1 expression promotes cytochrome c release into the cytosol, which activates the caspase cascade and induces apoptosis [20]. Based on these ndings, targeting Mcl-1 may represent a promising approach for treating OSCC.…”