**1. Introduction**

Cancer is currently the second leading cause of death globally [1–3]. While grea<sup>t</sup> strides have been made in the treatment of cancer in recent decades, we still face many open challenges to existing cancer therapies, such as adaptive resistance [4]. Throughout the development of human society, the importance of natural products [4–9] and their derivatives [10–12] in cancer treatment or prevention is supported by abundant evidence from cancer research [3,13,14], and give hopes to cancer patients.

The *Oleaceae* is a botanical family of woody dicotyledonous plants that are important in daily lives of many people due to their broad economic, food, and medicinal values. As previously

reported, a total of 232 secoiridoids (glycosides, aglycones, derivatives, and dimers) have been isolated from species in the *Oleaceae*. Multifloroside (**4**), together with 10-hydroxyoleoside 11-methyl ester (**1**), 10-hydroxyoleoside dimethyl ester (**2**), and 10-hydroxyligustroside (**3**), are 10-oxyderivatives of oleoside secoiridoid (Figure 1), and have been isolated from many *Oleaceae* plants, such as *Osmanthus asiaticus Nakai* [15], *Jasminum lanceolarium* Roxb [16,17], *Jasminum multiflorum* extract [18], and *Jasminum elongatum* (Bergius) Willd [19] (Figure 1). These four 10-oxyderivatives of oleoside secoiridoids (**1**–**4**) are similar in structure, with a hydroxyl substituent at 10 position, one of substituents, such as hydroxyl, methyl, *p*-hydroxy-phenylethyl, or *o*-hydroxy-*p*-hydroxy-phenylethyl, at 7 position, and one of substituents, such as methyl or *o*-hydroxy-*p*-hydroxy-phenylethyl, at 11 position.

**Figure 1.** Chemical structures of four 10-oxyderivative of oleoside secoiridoids (**1**–**4**) isolated from plants in the Oleaceae family. The images of the *Oleaceae* plants were downloaded from the Chinese Field Herbarium website (http://www.cfh.ac.cn/default.html).

No previous anti-cancer studies on **1**–**4** have been reported. Therefore, the study was basically aimed at helping us understand in vitro anti-cancer effect of **1**–**4** against the human epidermoid carcinoma cell lines A431 and the non-small cell lung cancer (NSCLC) cell lines A549. The structure-activity relationships (SAR) and their effect on cell colony formation, apoptosis, cell-cycle distribution, intracellular reactive-oxygen-species (ROS) generation, and the mitochondrial membrane potential (MMP) were also demonstrated in the present study.
